Biomarkers for posttransplantation outcomes

Paczesny, Sophie

doi:10.1182/blood-2018-02-791509

Cited by 63 publications

(51 citation statements)

References 106 publications

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“…For this reason, it is important that we establish clinical laboratory parameters that can be used to follow the response to ECP. In the past 5 years, several biomarkers emerged as useful predictors of chronic GvHD onset, severity, and therapy refractoriness; notably, suppression of tumorigenicity 2 (ST2), matrix metalloproteinase‐3 (MMP3), chemokine (C‐X‐C motif) ligand 9 (CXCL9), CXCL10, CXCL11, CD163, and B‐cell activating factor (BAFF) . In an effort to explore previously established chronic GvHD biomarkers in the context of ECP, we conducted a proof‐of‐principle study wherein clinical characteristics were systematically captured and serum was collected before ECP and at 2‐month intervals for 6 months for the purpose of biomarker testing.…”

Section: Introductionmentioning

confidence: 99%

Biomarker profiling of steroid-resistant chronic GvHD patients undergoing extracorporeal photopheresis demonstrates high ST2 levels at treatment onset and decline during therapy

Dunavin

Braun

et al. 2018

Adv Cell Gene Ther

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Chronic graft‐versus host disease (GvHD) affects approximately 30%‐70% of patients undergoing hematopoietic stem cell transplantation. Extracorporeal photopheresis (ECP) is an immunomodulatory therapy that is often used as a second‐line therapeutic option for steroid‐resistant chronic GvHD. There is a several week delay between the onset of ECP and clinical improvement in symptoms. Thus, a biomarker that precedes improvement in disease activity or predicts response to therapy would be of clinical value. In this study, we sought to determine how previously studied GvHD biomarkers change over a course of ECP therapy. Seven chronic GvHD biomarkers (ST2, MMP‐3, CXCL9, CXCL10, CXCL11, BAFF, and CD163) were measured by ELISA in 16 patients before and after 2 months of ECP. Initial ST2 levels were high compared to healthy donors and patient samples required more than the manufacturer‐recommended dilution. The median ST2 level decreased over the first 2 months of treatment (193 v. 96 ng/mL, P = 0.03); the other biomarkers did not change significantly. Serial ST2 levels at 2, 4, and 6 months after ECP initiation showed that ST2 levels declined over the course of therapy. The results of this study show that ST2 is substantially elevated and declines during therapy in patients who receive ECP as a second‐line therapy for chronic GvHD.

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Section: Introductionmentioning

confidence: 99%

Biomarker profiling of steroid-resistant chronic GvHD patients undergoing extracorporeal photopheresis demonstrates high ST2 levels at treatment onset and decline during therapy

Dunavin

Braun

et al. 2018

Adv Cell Gene Ther

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“…Significant progress has been made in identifying and validating biomarkers for GvHD (15). Based on the 2014 NIH consensus (16), these biomarkers have been investigated for diagnostic, prognostic, and predictive use, and additionally to assess treatment response.…”

Section: Overview Of Biomarkers In Gvhdmentioning

confidence: 99%

Extracorporeal Photopheresis (ECP) and the Potential of Novel Biomarkers in Optimizing Management of Acute and Chronic Graft vs. Host Disease (GvHD)

et al. 2020

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As the use of hematopoietic stem cell transplantation (HSCT) has become a more widespread and effective treatment for hematological malignant and non-malignant conditions, the need to minimize the harmful effects of graft-vs.-host disease (GvHD) has become more important in achieving good outcomes. With diagnosis of GvHD reliant on its clinical manifestations, research into biomarkers for the diagnosis, progression, and even for the prediction of disease, is imperative to combating the high levels of morbidity and mortality post-HSCT. Despite the development of novel treatment approaches to GvHD, corticosteroids remain the standard first-line treatment, with immunosuppressant therapies as second-line options. These strategies however have significant limitations and associated complications. Extracorporeal Photopheresis (ECP) has shown to be effective and safe in treating patients with symptomatic GvHD. ECP has been shown to have varied effects on multiple parts of the immune system and does not appear to increase the risk of relapse or infection in the post HSCT setting. Even so, ECP can be logistically more complex to organize and requires patients to be sufficiently stable. This review aims to summarize the potential role of biomarkers to help guide individualized treatment decisions in patients with acute and chronic GvHD. In relation to ECP, robust biomarkers of GvHD will be highly useful in informing patient selection, intensity and duration of the ECP schedule, monitoring of response and other treatment decisions alongside the concurrent administration of other GvHD therapies. Further research is warranted to establish how GvHD biomarkers are best incorporated into ECP treatment pathways with the goal of tailoring ECP to the needs of individual patients and maximizing benefit.

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“…Some biomarkers of aGVHD have already been described above while mentioning the technologies used to identify and validate them. Further, there are recent reviews that have described the most useful biomarkers . Therefore, we will just summarize the most promising focusing on biomarkers identified through clinical proteomics and those that had also been validated in one or more independent cohorts.…”

Section: Recent Validated Post‐transplantation Markersmentioning

confidence: 99%

Clinical Proteomics for Post‐Hematopoeitic Stem Cell Transplantation Outcomes

Paczesny

Metzger

2018

Proteomics Clinical Apps

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Allogeneic hematopoietic stem cell transplantation (HSCT) is the most effective form of tumor immunotherapy available to date. However, while HSCT can induce beneficial graft-versus-leukemia (GVL) effect, the adverse effect of graft-versus-host disease (GVHD), which is closely linked to GVL, is the major source of morbidity and mortality following HSCT. Until recently, available diagnostic and staging tools frequently fail to identify those at higher risk of disease progression or death. Furthermore, there are shortcomings in the prediction of the need for therapeutic interventions or the response rates to different forms of therapy. The past decade has been characterized by an explosive evolution of proteomics technologies, largely due to important advances in high-throughput MS instruments and bioinformatics. Building on these opportunities, blood biomarkers have been identified and validated both as promising diagnostic tools, prognostic tools that risk-stratify patients before future occurrence of GVHD and as predictive tools for responsiveness to GVHD therapy and non-relapse mortality. These biomarkers might facilitate timely and selective therapeutic intervention. This review summarizes current information on clinical proteomics for GVHD as well as other complications following HSCT. Finally, it proposes future directions for the translation of clinical proteomics to discovery of new potential therapeutic targets to the development of drugs.

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Biomarkers for posttransplantation outcomes

Cited by 63 publications

References 106 publications

Biomarker profiling of steroid-resistant chronic GvHD patients undergoing extracorporeal photopheresis demonstrates high ST2 levels at treatment onset and decline during therapy

Biomarker profiling of steroid-resistant chronic GvHD patients undergoing extracorporeal photopheresis demonstrates high ST2 levels at treatment onset and decline during therapy

Extracorporeal Photopheresis (ECP) and the Potential of Novel Biomarkers in Optimizing Management of Acute and Chronic Graft vs. Host Disease (GvHD)

Clinical Proteomics for Post‐Hematopoeitic Stem Cell Transplantation Outcomes

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